Increased mitochondrial mass in mitochondrial myopathy mice

Wredenberg, Anna; Wibom, Rolf; Wilhelmsson, Hans; Graff, Caroline; Wiener, Heidi H.; Burden, Steven J.; Oldfors, Anders; Westerblad, Håkan; Larsson, Nils‐Göran

doi:10.1073/pnas.232591499

Cited by 263 publications

(218 citation statements)

References 30 publications

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“…To compensate for reduced mitochondrial function with advancing age, cells increase mitochondrial density. This postulate is supported by previous studies showing that respiratory chain deficiency of mice induced the increase of mitochondrial mass (Wredenberg et al 2002) and the loss of ΔΨm induced mitochondrial biogenesis (Passos et al 2007). In addition, this phenomenon may reflect the lower function of cellular degradation system with advancing age.…”

Section: Mitochondrial Densitysupporting

confidence: 72%

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Chuang

Hsu

2012

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Trophocytes and fat cells in honeybees (Apis mellifera) have served as targets for cellular senescence studies, but mitochondrial energy utilization with advancing age in workers is unknown. In this study, mitochondrial energy utilization was evaluated in the trophocytes and fat cells of young and old workers reared in a field hive. The results showed that (1) mitochondrial density increased with advancing age; (2) mitochondrial membrane potential (ΔΨm), nicotinamide adenine dinucleotide oxidized form (NAD + ) concentration, adenosine triphosphate (ATP) concentration, and NAD + /nicotinamide adenine dinucleotide reduced form (NADH) ratio decreased with advancing age; and (3) the expression of NADH dehydrogenase 1 (ND1), ATP synthase, and voltage-dependent anion channel 1 (VDAC1) increased with advancing age, whereas ND1 and ATP synthase did not differ with advancing age after normalization to mitochondrial density and VDAC1. These results show that the trophocytes and fat cells of young workers have higher mitochondrial energy utilization efficiency than those of old workers and that aging results in a decline in mitochondrial energy utilization in the trophocytes and fat cells of worker honeybees.

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Section: Mitochondrial Densitysupporting

confidence: 72%

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Chuang

Hsu

2012

AGE

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“…[3][4][5][6] The reason underlying this phenomenon remained elusive. We found that age-related mitophagy decline causes progressive accumulation of mitochondria in the nematode Caenorhabditis elegans.…”

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confidence: 99%

Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis

2015

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Mitochondria, the main energy hub of the cell, are highly dynamic organelles, playing essential roles in fundamental cellular processes. Mitochondrial function impinges on several signalling pathways modulating cellular metabolism, cell survival and healthspan. Accordingly, impairment of mitochondria has been associated with numerous pathological conditions and ageing. Maintenance of cellular and organismal homeostasis thus hinges on fine-tuning mitochondrial quality control. Mitochondrial biogenesis and mitochondrial selective autophagy (mitophagy), two opposing cellular pathways, coordinately regulate mitochondrial content to sustain energy metabolism, in response to cellular metabolic state, stress and other intracellular or environmental signals. It is not surprising, therefore, that disequilibrium or imbalance between mitochondrial proliferation and degradation processes underlies the onset and progressive unfolding of several pathological conditions in humans, including neurodegenerative diseases, myopathies and other age-associated disorders.Mitochondrial biogenesis is a complex and multistep cellular process, which involves mtDNA transcription and translation, translation of transcripts derived from nucleus, recruitment of newly synthesized proteins and lipids, import and assembly of mitochondrial and nuclear products in the expanding mitochondrial network. Spatiotemporal control of mitochondrial biogenesis is mediated by numerous transcription factors in response to diverse stimuli, including both intracellular signals and environmental stimuli (nutrient availability, growth factors and hormones, toxins, temperature and oxygen fluctuations, among others). The master regulator of mitochondrial energy metabolism is the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), the best-studied member of the peroxisome proliferator activated receptor family of transcription co-activators, which orchestrates the activity of several transcription factors involved in mitochondrial biogenesis and function. 1 These include the nuclear respiratory factors (NRF1 and NRF2), the estrogen-related receptors (ERR-α, -β and -γ) and the nuclear factor erythroid 2-related factor 2 (NRF2/NFE2L2) that are part of a complex transcriptional network that regulates mitochondrial biogenesis and energy metabolism. 1,2 Alongside their essential roles in cell and animal physiology, mitochondria are also the major source of potentially hazardous reactive oxygen species as by-products of respiration. Thus, eukaryotic cells have evolved a wide arsenal of quality control mechanisms to preserve mitochondrial homeostasis and prevent cellular damage and eventual death. Mitophagy, a selective type of autophagy, is triggered upon accumulation of damaged or superfluous mitochondria. Dysfunctional mitochondria are targeted and engulfed by double-membrane vesicles known as autophagosomes and are transferred for degradation in lysosomes. Cells induce mitophagy to regulate the size and quality of their mitochondrial network...

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“…Gene expression studies of respiratory chaindeficient budding yeast cells have demonstrated a variety of responses, including major reconfiguration of the metabolic pathways and induction of peroxisomal biogenesis (6). We have generated mouse models for studies of the pathogenesis of respiratory chain deficiency in vivo by using a conditional knockout strategy to disrupt the mitochondrial transcription factor A (Tfam) gene in selected cell types (7)(8)(9)(10)(11)(12). Increased cell death is a common consequence of prolonged respiratory chain deficiency, with the mechanism for cell death induction differing between affected tissues (8,9,13,14).…”

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confidence: 99%

A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts

Hansson

Hance

Dufour

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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We performed global gene expression analyses in mouse hearts with progressive respiratory chain deficiency and found a metabolic switch at an early disease stage. The tissue-specific mitochondrial transcription factor A (Tfam) knockout mice of this study displayed a progressive heart phenotype with depletion of mtDNA and an accompanying severe decline of respiratory chain enzyme activities along with a decreased mitochondrial ATP production rate. These characteristics were observed after 2 weeks of age and became gradually more severe until the terminal stage occurred at 10 -12 weeks of age. Global gene expression analyses with microarrays showed that a metabolic switch occurred early in the progression of cardiac mitochondrial dysfunction. A large number of genes encoding critical enzymes in fatty acid oxidation showed decreased expression whereas several genes encoding glycolytic enzymes showed increased expression. These alterations are consistent with activation of a fetal gene expression program, a well-documented phenomenon in cardiac disease. An increase in mitochondrial mass was not observed until the disease had reached an advanced stage. In contrast to what we have earlier observed in respiratory chain-deficient skeletal muscle, the increased mitochondrial biogenesis in respiratory chain-deficient heart muscle did not increase the overall mitochondrial ATP production rate. The observed switch in metabolism is unlikely to benefit energy homeostasis in the respiratory chain-deficient hearts and therefore likely aggravates the disease. It can thus be concluded that at least some of the secondary gene expression alterations in mitochondrial cardiomyopathy do not compensate but rather directly contribute to heart failure progression.

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Increased mitochondrial mass in mitochondrial myopathy mice

Cited by 263 publications

References 30 publications

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis

A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts

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